Transition metal complexes nucleotides

Building towards models relevant for polymeric DNA and RNA, nucleotides contain a phosphate attached at the 5 or 3 position. The 5 -nucleotides are most commonly studied, for which the phosphate has a pAa 6 for the first protonation step. Unless otherwise noted, throughout this chapter nucleotide will refer to the 5 -phosphate linkage. In nucleotides, metal-phosphate coordination competes with metal-base interactions. Chelate complexes with both phosphate and base coordination can occur when sterically allowed. Thus, transition metal complexes with purine monophosphates tend to exhibit metal coordination to the base N7 position, with apparent hydrogen bonding of coordinated waters to the phosphate. By contrast, more ionic Mg" binds preferentially to the phosphate groups in nucleotide monophosphates. In di- and tri-phosphate complexes such as metal-ATP compounds, the proximity of multiple phosphates generally favors polyphosphate chelate complexes with metal ions. 

Polarographic studies are reported on thioesters, mainly of the type (140) and (141), and on trichloroethylphosphonites. In the field of nucleotides and nucleosides it is found that ATP has a very high surface activity at the mercury electrode, which is strongly dependent upon complex formation with transition metals. The polarographic behaviour of cobalt complexes with triphenylphosphine and its oxide has been studied in order to estimate extraction efficiencies. 

This method is especially suitable for studies with polymer nucleotide-metal ion interaction. When dissolved nucleic acids are exposed with and without metal ions to an increase of temperature structural changes, some reversible, some irreversible can be observed (27, 24, 27, 30, 39, 54—56, 75, 100, 108). The two parameters Tm (or midpoint of the transition) and a (the width of the transition) allow conclusions about conformational alterations. The application of this procedure for quantitative studies of metal complexing still needs to be elucidated. 

Fig. 2.8. Factors controlling the production of free radicals in cells and tissues (Rice-Gvans, 1990a). Free radicals may be generated in cells and tissues through increased radical input mediated by the disruption of internal processes or by external influences, or as a consequence of decreased protective capacity. Increased radical input may arise through excessive leukocyte activation, disrupted mitochondrial electron transport or altered arachidonic acid metabolism. Delocalization or redistribution of transition metal ion complexes may also induce oxidative stress, for example, microbleeding in the brain, in the eye, in the rheumatoid joint. In addition, reduced activities or levels of protectant enzymes, destruction or suppressed production of nucleotide coenzymes, reduced levels of antioxidants, abnormal glutathione metabolism, or leakage of antioxidants through damaged membranes, can all contribute to oxidative stress.

The coordination properties of the nucleobases have been reviewed by Houlton (40) and by Lippert (2). In a recent review, Lippert discussed the influence of the metal coordination on the piSTa of the nucleobases (41), which correlates with their coordination properties. While the coordination properties of nucleobases, nucleosides, and nucleotides have been extensively studied and reviewed, the number of articles dedicated to the coordination properties of nucleic acids is signihcantly smaller. DeRose et al. (42) recently published a systematic review of the site-specific interactions between both main group and transition metal ions with a broad range of nucleic acids from 10 bp DNA duplexes to 300 00 nucleotide RNA molecules as well as with some nucleobases, nucleosides, and nucleotides. They focused on results obtained primarily from X-ray crystallographic studies. Egli also presented information on the metal ion coordination to DNA in reviews dedicated to X-ray studies of nucleic acids (43, 44). Sletten and Fr0ystein (45) reviewed NMR studies of the interaction between nucleic acids and several late transition metal ions and Zn. Binding of metal complexes to DNA by n interactions has been reviewed by Dupureur and Barton (46). 

The majority of described metal-nucleotide or oligonucleotide complexes come from studies with transition metals, predominantly those late in the series. Because of similar ionic radius and... 

As early as 1932 it was reported that an increase in the acidity of AMP was observed when borate was present [46). Twenty years later the complex reactions of borate with nucleosides were employed to separate mixtures of nucleosides and even nucleotides (see also sections on chromatography and electrophoresis). Only very little is known about whether or not borate interferes with biochemical reactions where nucleosides or nucleotides are involved. Thus, the stability constants of some boric nucleosides (72) are roughly in the same order of magnitude as the formation constants of earth alkaline or transition metal nucleotide complexes (62). It is therefore not unlikely that borate could influence to... 

In contrast to Mg + and Mn +, which stabilize secondary structures in DNA and RNA, Cu + destabilizes DNA and RNA double helices, and this is attributed to the ability of copper to bind to the nucleic acid bases. Chao and Kearns have recently explored the possibility that this binding, as detected by electron and nuclear magnetic resonance spectroscopy, might be used to probe certain structural features of nucleic acid molecules, such as the looped out regions of tRNAs. The nature of the Cu complexes formed with nucleosides and nucleotides varies with the specific nucleic acid derivatives used and also the pH. Thus, in the pH range 8.5—10.0, copper forms a water-soluble complex with the ribose OH groups of the ribonu-cleosides and 5 -ribonucleotides, but these complexes cannot form with any of the deoxynucleosides or the 2 - and 3 -ribonucleotides. It is suggested that copper(ii) could stabilize unusual polynucleotide structures or interactions in certain enzymatic systems the latter could, for example, be responsible for translational errors in the RNA,DNA polymerase system which are known to be induced by transition metals. 

In this work, well-defined complexes of biologically important 3d transition metals (Cu(II), Fe(III), Fe(II), and Ni(II)) with either neutral or monodeprotonated anionic adenine or adenosine, synthesized and characterized 5 as described previously, have been used as a model system to study the effects of the interaction of transition metals with purine and purine nucleoside components of nucleic acids on redox properties of the system. The structures of the complexes is simpler than that of nucleic acids and facilitates evaluation of the electrochemical results. The non-phosphorylated monomeric units are suitable model ligands as the use of nucleotides offers complicating factors associated with phosphate due to self-association and self-complexation and preference for the PO4 moiety as the site for complexation. ... 

Structure of binary complexes of mono- and poly-nucleotides with metal ions of the first transition group. H. Pezzano and F. Podo, Chem. Rev., 1980, 80, 365-401 (389). 

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